Intermediate filaments in malignant melanomas. Identification and use as marker in surgical pathology.

Ramaekers, F.C.S.; Puts, J. J. G.; Moesker, O.; Kant, A.; Vooijs, G. P.; Jap, P. H. K.

doi:10.1172/jci110810

Cited by 50 publications

(14 citation statements)

References 33 publications

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“…[13][14][15] The earliest immunohistochemical studies of melanoma, performed chiefly by immunofluorescence on fresh, frozen tissues, showed melanocytes and melanomas to express only vimentin. [16][17][18] Gatter et al 19 These investigators also demonstrated with western blot that keratin-immunoreactive melanomas were truly producing keratin peptides. Interestingly, Zarbo et al 6 were only able to find aberrant keratin expression in recurrent or metastatic melanomas.…”

Section: Discussionmentioning

confidence: 96%

Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases

2015

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Malignant melanomas are known to express vimentin, among other intermediate filaments. Though anomalous keratin expression by malignant melanoma has been reported, its frequency is not well-established and this phenomenon is not well-known. We have seen in consultation a number of malignant melanomas with anomalous expression of keratin, other intermediate filaments, or synaptophysin, and therefore studied a large group of primary and metastatic melanomas to determine the frequency of these events. About 73 cases of malignant melanoma (22 primaries and 51 metastases) from 71 patients (51 male, 20 female; mean 59 years, range 17-87 years) were retrieved from our archives. Prior diagnoses were confirmed by re-review of hematoxylin and eosin sections and relevant (e.g., S100 protein, HMB45, Melan-A, and tyrosinase) immunohistochemical studies. Available sections were immunostained for keratin (OSCAR and AE1/AE3 antibodies), desmin, neurofilament protein, glial fibrillary acidic protein, synaptophysin, and chromogranin A. Not all cases could be tested for all markers. Cases were predominantly epithelioid (48/73, 66%) or spindle cell/desmoplastic (25/73, 34%). S100 protein, Melan-A, HMB45, and tyrosinase were positive in 60/65 (92%), 34/64 (53%), 30/60 (50%), 25/48 (52%) of cases, respectively. All five S100-protein-negative cases expressed at least one of the other melanocytic markers: Melan-A (two of four, 50%), HMB45 (two of three, 67%), and tyrosinase (one of two, 50%). All cases expressed at least one melanocytic marker. Cases were positive for keratin (OSCAR, 17/61, 28%; AE1/AE3, 16/40, 40%), desmin (11/47, 24%), neurofilament protein (5/31, 16%), glial fibrillary acidic protein (3/32, 9%), and synaptophysin (10/34, 29%), typically only in a minority of cells. Chromogranin was negative (0/32, 0%).

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Section: Discussionmentioning

confidence: 96%

Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases

2015

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“…20,23 In a previous study, tumor cells of melanomas of Duroc pigs were vimentin ϩ and cytokeratin Ϫ . 12 The majority of pigmented macrophages expressed vimentin and A1AT, and all of them were cytokeratin Ϫ and S100 Ϫ , an immunophenotype reported for human macrophages.…”

Section: Discussionmentioning

confidence: 95%

Immunohistochemical Characterization of Tumor Cells and Inflammatory Infiltrate Associated with Cutaneous Melanocytic Tumors of Duroc and Iberian Swine

et al. 2002

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Abstract. The immunophenotype of tumor cells and inflammatory infiltrate associated with cutaneous melanocytic lesions (29 melanocytomas, two malignant melanomas, and 23 residual lesions) from 54 adult Iberian and Iberian ϫ Duroc pigs were examined using a panel of nine antibodies. All neoplastic cells were vimentin ϩ , cytokeratin Ϫ , and alpha-1-antitrypsin Ϫ and the majority were S100 ϩ , whereas all pigmented macrophages were vimentin ϩ , cytokeratin Ϫ , and S100 Ϫ and most expressed alpha-1-antitrypsin. Regressing tumors were characterized by zones with low density of neoplastic cells accompanied by heavy infiltration of CD3 ϩ T lymphocytes, whereas zones with high density of neoplastic cells showed very low numbers of CD3 ϩ T lymphocytes. The infiltrate of CD79a ϩ B cells and IgG, IgM, and IgA plasma cells was low. The majority of lymphocytes of the peri-and intratumoral infiltrate were major histocompatibility complex class II ϩ , but neoplastic cells did not express class II antigen. The 17 residual lesions examined were composed of macrophages containing abundant melanin pigment and low to moderate numbers of CD3 ϩ T lymphocytes. The results of the present study suggest that the local cellular immune response plays a crucial role in the host response that induces regression of cutaneous melanomas and melanocytomas of the Iberian and crossbred Iberian ϫ Duroc pigs.Key words: Immunohistochemistry; melanoma; skin; swine; tumor regression.Certain breeds of swine such as Duroc, Sinclair, and Hormel have a hereditary predisposition to develop cutaneous melanocytic tumors, 11,12,15 whereas these tumors are rare in other swine breeds. 22,28 Swine melanocytomas are more often reported than are malignant melanomas, which may metastasize to lymph nodes or internal organs. Both swine melanocytomas and malignant melanomas are often obvious at birth or develop early in life. 15,28 Melanomas of Sinclair miniature swine often regress spontaneously; regression is often accompanied by intense intra-and peritumoral infiltration of macrophages and lymphocytes. Thus, melanoma in Sinclair swine is considered an excellent animal model for study of the immunologic mechanisms involved in tumor regression. 10,15,18,21 Recently, an extremely high prevalence of melanocytic lesions was reported in 3,176 crossbred Iberian ϫ Duroc pigs and purebred Iberian pigs. 7 In this population, 95% of pigs had cutaneous lesions, 16% had hyperpigmentation in the oral cavity, 10% had lesions of the mediastinal lymph nodes, and 9% had lesions in the thymus. Only 0.15% of the cutaneous melanocytic lesions were malignant melanomas, whereas the remainder were either melanocytomas (often showing signs of regression and abundant lymphocytic infiltration) or residual lesions. 7 This high prevalence of swine cutaneous melanocytic lesions has not been reported before, but familial predisposition was suspected because these lesions have been reported in Duroc pigs 11,12 and all pigs were from the same geographic region (north of the province of Cordoba, An...

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“…Expression of vimentin is well-recognized in normal melanocytes and human uveal melanoma cells [29]. For some time, vimentin was believed to be the only intermediate filament type present in these cells [30,31]. However, more recent studies have shown that keratin, another intermediate filament, is also expressed in malignant cutaneous melanoma cells [32] and uveal melanoma cells [18,33].…”

Section: Discussionmentioning

confidence: 99%

Clinical and histopathological features and immunoreactivity of human choroidal and ciliary melanomas as prognostic factors for metastasis and death

Simões

Call

Corrêa

et al. 2011

Graefes Arch Clin Exp Ophthalmol

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Intermediate filaments in malignant melanomas. Identification and use as marker in surgical pathology.

Cited by 50 publications

References 33 publications

Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases

Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases

Immunohistochemical Characterization of Tumor Cells and Inflammatory Infiltrate Associated with Cutaneous Melanocytic Tumors of Duroc and Iberian Swine

Clinical and histopathological features and immunoreactivity of human choroidal and ciliary melanomas as prognostic factors for metastasis and death

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